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Phase II Trial of Carboplatin +/- Tocilizumab for Metastatic Triple Negative and ER-low Breast Cancers

Primary Purpose

Metastatic Breast Cancer, Triple Negative Breast Cancer, Estrogen-receptor-low Breast Cancer

Status
Not yet recruiting
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Carboplatin
Tocilizumab
Sponsored by
Kathy Miller
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Metastatic Breast Cancer focused on measuring Breast Cancer, Phase II

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria: ≥ 18 years old at the time of informed consent Ability to provide written informed consent and HIPAA authorization Locally recurrent (not amenable to local therapy with curative intent) or metastatic breast cancer that is triple negative or ER-low (ER and PR ≤ 9% weak staining) No prior chemotherapy for metastatic disease a. Prior (neo)adjuvant therapy must have been completed at least 12 months from diagnosis of unresectable locally recurrent or metastatic disease. Measurable disease based on RECIST 1.1 criteria. Disease amenable to and consent for study-specific biopsy a. NOTE: If no disease amenable to biopsy is present at the time of second biopsy, subjects may continue participation in the study and further study specific biopsies will not be required. ECOG PS 0 or 1 Patients with treated, asymptomatic CNS disease may participate if the patient is > 4 weeks from completion of CNS therapy (radiation and/or surgery), is clinically stable at the time of study entry, and is receiving a stable or decreasing dose of corticosteroid therapy. Brain MRI or head CT is required at screening for patients with known brain metastases. Adequate organ function as indicated by: Total bilirubin < ULN (except in patients with documented Gilbert's disease, who must have a total bilirubin < 3.0 mg/dL) Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) < 5.0 x ULN Creatinine clearance of > 50 mL/min using the Cockcroft-Gault formula Absolute neutrophil count (ANC) > 1.5 K/mm3 Platelets > 100 K/ mm3 Hgb > 9.0 g/dL Women of childbearing potential must have a negative pregnancy test within 14 days of protocol registration. Women are considered to have childbearing potential (regardless of sexual orientation, having undergone a tubal ligation, or remaining celibate by choice) unless they meet one of the following criteria: Has undergone a hysterectomy or bilateral oophorectomy; or Has been naturally amenorrheic for at least 24 consecutive months. Women of childbearing potential and men must agree to use effective contraception throughout the study and for 6 months after the last study treatment. Note: Acceptable methods of birth control include abstinence, partner with previous vasectomy, placement of an intrauterine device (IUD), condom with spermicidal foam/gel/film/cream/suppository, diaphragm or cervical vault cap, or hormonal birth control (pills or injections). Exclusion Criteria: Prior treatment with or known contraindication to treatment with tocilizumab or other IL-6/IL-6R targeted agent Patients who are PD-L1 positive (CPS ≥ 10), unless they have a clear contraindication to pembrolizumab therapy. Active infection requiring parenteral antibiotics Concurrent use of methotrexate or systemic corticosteroids Active or symptomatic CNS disease Patients with HER2+ disease HER2 will be considered positive if scored 3+ by immunohistochemistry (IHC) or 2+ by IHC associated with a fluorescence in situ hybridization (FISH) ratio of > 2.0 or > 6 total HER2 gene copies per cell. Patients with active malignancy other than breast cancer. Patients with prior malignancies without recurrence after standard treatment will not be excluded Radiation therapy within 2 weeks of registration Hormone therapy within 2 weeks of registration

Sites / Locations

  • IU Health Joe and Shelly Schwarz Cancer Center
  • Indiana University Melvin and Bren Simon Comprehensive Cancer Center
  • Sidney and Lois Eskenazi Hospital

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Active Comparator

Experimental

Active Comparator

Experimental

Arm Label

Black Monotherapy

Black Combination treatment

Non-Black Monotherapy

Non-Black Combination treatment

Arm Description

Outcomes

Primary Outcome Measures

Overall response rate
Efficacy of tocilizumab in Black and non-Black patients
efficacy defined as using the difference in difference approach across race based cohorts
Progression-free survival

Secondary Outcome Measures

Safety of carboplatin monotherapy compared to carboplatin combined with tocilizumab using National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v 5.0
Evaluate the differences in inflammatory pathways between Black and non-Black patients
Tumor PZP, IL-6, and phosphoSTAT3
Evaluate the impact of Duffy genotype on efficacy in Black patients
Tumor PZP, IL-6, and phosphoSTAT3 between Duffy-null, Duffy-heterozygous, and Duffy-wild type

Full Information

First Posted
April 27, 2023
Last Updated
October 10, 2023
Sponsor
Kathy Miller
Collaborators
Genentech, Inc.
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1. Study Identification

Unique Protocol Identification Number
NCT05846789
Brief Title
Phase II Trial of Carboplatin +/- Tocilizumab for Metastatic Triple Negative and ER-low Breast Cancers
Official Title
A Phase II Trial of Carboplatin +/- Tocilizumab as Initial Therapy for Metastatic Triple Negative and ER-low Breast Cancers
Study Type
Interventional

2. Study Status

Record Verification Date
October 2023
Overall Recruitment Status
Not yet recruiting
Study Start Date
November 2023 (Anticipated)
Primary Completion Date
June 2025 (Anticipated)
Study Completion Date
June 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor-Investigator
Name of the Sponsor
Kathy Miller
Collaborators
Genentech, Inc.

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
This is a randomized Phase II study of carboplatin monotherapy vs. carboplatin combined with tocilizumab in in Black and non-Black patients with metastatic triple negative or ER low breast cancer.
Detailed Description
Randomized phase II using a two-stage Bayesian optimal phase II two-arm design (BOP2). Patients are randomized 1:1 to either the monotherapy or combination arms. This requires 42 patients (21 per treatment arm) in stage I for each race-based cohort. If the no. of response in experimental - no. of response in control is no greater than -1, the trial is early stopped at stage I for futility. Otherwise, additional 42 patients for each race-based cohort will be enrolled and randomized to the study in stage II.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Metastatic Breast Cancer, Triple Negative Breast Cancer, Estrogen-receptor-low Breast Cancer
Keywords
Breast Cancer, Phase II

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Model Description
Patients are stratified by either Black or non-Black (race-based cohort) and are then randomized 1:1 to either the monotherapy or combination arm. This requires 42 patients (21 per treatment arm) in stage I for each race-based cohort. If the no. of response in experimental - no. of response in control is no greater than -1, the trial is early stopped at stage I for futility. Otherwise, additional 42 patients for each race-based cohort will be enrolled and randomized to the study in stage II for a total of 168 subjects across all 4 arms.
Masking
None (Open Label)
Allocation
Randomized
Enrollment
168 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Black Monotherapy
Arm Type
Active Comparator
Arm Title
Black Combination treatment
Arm Type
Experimental
Arm Title
Non-Black Monotherapy
Arm Type
Active Comparator
Arm Title
Non-Black Combination treatment
Arm Type
Experimental
Intervention Type
Drug
Intervention Name(s)
Carboplatin
Intervention Description
Carboplatin will be given AUC 6 IV q3 weeks for a maximum of 9 infusions.
Intervention Type
Drug
Intervention Name(s)
Tocilizumab
Intervention Description
Tocilizimab 8 mg/ actual body weight in kg IV q4 weeks
Primary Outcome Measure Information:
Title
Overall response rate
Time Frame
through study completion (i.e. up to 2 years)
Title
Efficacy of tocilizumab in Black and non-Black patients
Description
efficacy defined as using the difference in difference approach across race based cohorts
Time Frame
through study completion (i.e. up to 2 years)
Title
Progression-free survival
Time Frame
through study completion (i.e. up to 2 years)
Secondary Outcome Measure Information:
Title
Safety of carboplatin monotherapy compared to carboplatin combined with tocilizumab using National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v 5.0
Time Frame
through study completion (i.e. up to 2 years)
Title
Evaluate the differences in inflammatory pathways between Black and non-Black patients
Description
Tumor PZP, IL-6, and phosphoSTAT3
Time Frame
Baseline
Title
Evaluate the impact of Duffy genotype on efficacy in Black patients
Description
Tumor PZP, IL-6, and phosphoSTAT3 between Duffy-null, Duffy-heterozygous, and Duffy-wild type
Time Frame
Baseline

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: ≥ 18 years old at the time of informed consent Ability to provide written informed consent and HIPAA authorization Locally recurrent (not amenable to local therapy with curative intent) or metastatic breast cancer that is triple negative or ER-low (ER and PR ≤ 9% weak staining) No prior chemotherapy for metastatic disease a. Prior (neo)adjuvant therapy must have been completed at least 12 months from diagnosis of unresectable locally recurrent or metastatic disease. Measurable disease based on RECIST 1.1 criteria. Disease amenable to and consent for study-specific biopsy a. NOTE: If no disease amenable to biopsy is present at the time of second biopsy, subjects may continue participation in the study and further study specific biopsies will not be required. ECOG PS 0 or 1 Patients with treated, asymptomatic CNS disease may participate if the patient is > 4 weeks from completion of CNS therapy (radiation and/or surgery), is clinically stable at the time of study entry, and is receiving a stable or decreasing dose of corticosteroid therapy. Brain MRI or head CT is required at screening for patients with known brain metastases. Adequate organ function as indicated by: Total bilirubin < ULN (except in patients with documented Gilbert's disease, who must have a total bilirubin < 3.0 mg/dL) Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) < 5.0 x ULN Creatinine clearance of > 50 mL/min using the Cockcroft-Gault formula Absolute neutrophil count (ANC) > 1.5 K/mm3 Platelets > 100 K/ mm3 Hgb > 9.0 g/dL Women of childbearing potential must have a negative pregnancy test within 14 days of protocol registration. Women are considered to have childbearing potential (regardless of sexual orientation, having undergone a tubal ligation, or remaining celibate by choice) unless they meet one of the following criteria: Has undergone a hysterectomy or bilateral oophorectomy; or Has been naturally amenorrheic for at least 24 consecutive months. Women of childbearing potential and men must agree to use effective contraception throughout the study and for 6 months after the last study treatment. Note: Acceptable methods of birth control include abstinence, partner with previous vasectomy, placement of an intrauterine device (IUD), condom with spermicidal foam/gel/film/cream/suppository, diaphragm or cervical vault cap, or hormonal birth control (pills or injections). Exclusion Criteria: Prior treatment with or known contraindication to treatment with tocilizumab or other IL-6/IL-6R targeted agent Patients who are PD-L1 positive (CPS ≥ 10), unless they have a clear contraindication to pembrolizumab therapy. Active infection requiring parenteral antibiotics Concurrent use of methotrexate or systemic corticosteroids Active or symptomatic CNS disease Patients with HER2+ disease HER2 will be considered positive if scored 3+ by immunohistochemistry (IHC) or 2+ by IHC associated with a fluorescence in situ hybridization (FISH) ratio of > 2.0 or > 6 total HER2 gene copies per cell. Patients with active malignancy other than breast cancer. Patients with prior malignancies without recurrence after standard treatment will not be excluded Radiation therapy within 2 weeks of registration Hormone therapy within 2 weeks of registration
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Xin Bryan, RN
Phone
317-274-5495
Email
zhongx@iupui.edu
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Kathy Miller, MD
Organizational Affiliation
Indiana University
Official's Role
Principal Investigator
Facility Information:
Facility Name
IU Health Joe and Shelly Schwarz Cancer Center
City
Carmel
State/Province
Indiana
ZIP/Postal Code
46032
Country
United States
Facility Name
Indiana University Melvin and Bren Simon Comprehensive Cancer Center
City
Indianapolis
State/Province
Indiana
ZIP/Postal Code
46202
Country
United States
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Xin Bryan, RN
Phone
317-274-5495
Email
zhongx@iupui.edu
First Name & Middle Initial & Last Name & Degree
Kathy Miller, MD
Facility Name
Sidney and Lois Eskenazi Hospital
City
Indianapolis
State/Province
Indiana
ZIP/Postal Code
46202
Country
United States

12. IPD Sharing Statement

Learn more about this trial

Phase II Trial of Carboplatin +/- Tocilizumab for Metastatic Triple Negative and ER-low Breast Cancers

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